DESCRIPTION (provided by investigator): The results of ecological studies and animal experiments suggest that high levels of vitamin D may prevent multiple sclerosis (MS), but there are no prospective epidemiological data addressing this hypothesis. The investigators propose to conduct a nested case-control study to determine prospectively the relation between vitamin D status and risk of developing MS. The primary aim of the investigation is to determine whether circulating levels of 25-Hydroxyvitamin D measured in healthy young adults predict the future risk of developing MS. The source population of the proposed study includes over 3 million US Army and Navy personnel whose blood samples are stored in the Department of Defense (DOD) Serum Repository. The identification of cases of MS in this population is ongoing; by the end of January 2003 we confirmed 149 incident cases of MS in the Army with onset of first neurological symptoms after the date of blood collection and we expect to confirm 173 MS cases occurring between January 1, 2000 and December 31,2003 in the Navy. The estimated interval between blood collection and MS onset will be on average 4 years and repeated blood samples collected from the same person before MS onset will be available for over 80 percent of the cases. For each case, two controls matched by age, gender, ethnicity, and time of blood collection will be selected from the source population. The proposed study is unique in relying on a large series of cases with blood collected several years before the onset of symptoms. Further, the availability of repeated samples for the same individuals will permit a better assessment of long-term circulating vitamin D levels and adjustment for seasonal variations. The finding of an inverse association between 25-OH D in serum and risk of MS would provide strong support for a role of vitamin D in the prevention of MS. On the other hand, the lack of such association would suggest that other hypotheses need to be addressed to explain the strong latitude gradient in MS incidence. [unreadable] [unreadable]